When cells are exposed to potentially harmful agents (termed stressors) such as heat, a family of genes is activated to produce a small number of proteins (termed stress proteins). One consequence of this response to stressors is the establishment in cells of a state of tolerance to otherwise lethal stresses. Virus infections are often accompanied by the induction of interferon (a natural pyrogen) and fever. And, some viruses can induce stress proteins. Thus, virus infection may take place in a phenotypically altered host -- the stressed cell. This study is based on the postulate that the disease state produced by viruses may be modified in cells exposed to stressors. Consequently, this study will determine whether the course of virus infection and the action of the interferon system is altered in cells induced to contain stress proteins by: (1) Determining the relationship between stressed-cells and the interferon system. (2) Defining the development of thermotolerance in virus-infected cells. (3) Studying stressed-cells as hosts for Vesicular Stomatitis virus, as a model virus. (4) Determining the role of the stressed-cell in the selection of ts-mutants during persistent infection. (5) Defining the role of stressed-cells in the generation and action of defective-interfering virus particles. The results obtained from this study should contribute to our understanding of how viruses, interferon and the stress protein response may affect disease systems at the level of individual infected cells expressing both the stressed-cell state and the actions of interferon.